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Background: Ischemia-modified albumin (IMA) has been shown to be elevated in patients after percutaneous coronary intervention (PCI). Our goal was to investigate the association between IMA levels and left ventricular ejection fraction in patients with ST-segment elevation myocardial infarction (STEMI) treated with PCI and who developed heart failure during their Coronary Care Unit (CCU) stay., Methods: We assessed 75 patients with a first STEMI. Presence of heart failure was assessed during CCU admission, and patients were subdivided into 2 groups: group A (n=45) comprised patients in Killip class I, and group B (n=30) Killip classes>I. Serum IMA concentration was measured within the first 15 min post-PCI. The IMA measured was performed using an indirect method based in the Albumin Cobalt Binding (ACB) colorimetric assay. The ideal cutoff value of IMA was calculated by the receiver operating characteristic (ROC) curve analysis., Results: Serum IMA concentrations were significantly higher in group B than in group A (0.37+/-0.09 vs 0.30+/-0.06 (A.U.); p<0.0001). The sensitivity and specificity of IMA for heart failure were 93.3% and 37.7%, respectively, at 0.31 A.U. Multivariable adjustment IMA showed a significant inverse correlation with left ventricular ejection function (r=-0.32; p=0.004). On multivariable analysis both IMA (OR=2.1, 95%CI: 1.2 to 3.9, p<0.001) and left ventricular ejection function (OR=1.7, 95%CI: 1.1 to 2.1, p<0.01) correlated with the occurrence of heart failure., Conclusion: In patients with STEMI undergoing PCI, serum IMA concentrations are significantly related to LVEF and represent an early marker of left ventricular dysfunction.

Introduction: The purpose of this study was to compare serum matrix metalloproteinase (MMP)-9 levels in a population of type 2 diabetic versus non-diabetic patients hospitalized with ST-segment elevation myocardial infarction (STEMI) and to examine the relationship between serum MMP-9 levels and the incidence of in-hospital cardiac events, including death and cardiogenic shock., Methods: We recruited 120 patients with STEMI, of whom 48 were type 2 diabetic and 72 non-diabetic. Serum MMP-9 levels were measured on admission, using a commercially available ELISA. The primary study endpoint was cardiac death in-hospital and cardiogenic shock., Results: Mean serum MMP-9 levels were significantly higher in type 2 diabetic patients compared to non-diabetic patients (240+/-52 ng/mL versus 185+/-47 ng/mL; P<0.0001). In multivariable analysis, type 2 diabetes was an independent factor for mortality [OR: 1.75 (1.40-2.30); P=0.005] and cardiogenic shock [OR: 1.55 (1.20-1.70); P=0.03] when the variable MMP-9 level was not introduced into the model, but it was less significantly associated with mortality [OR: 1.60 (1.40-2.10); P=0.01] and no longer associated with cardiogenic shock when MMP-9 was in the model., Conclusion: After STEMI, type 2 diabetes is independently associated with high serum MMP-9 levels. This elevated MMP-9 is strongly associated with the increased incidence of in-hospital mortality and cardiogenic shock observed in type 2 diabetes. Our findings clearly indicate that serum MMP-9 provides a highly valuable prognostic information on in-hospital outcome after STEMI, in particular in type 2 diabetic patients.

Elevated levels of soluble cellular adhesion molecules have been reported in patients with acute coronary syndromes. Likewise, a relation between decreased nocturnal melatonin levels and coronary artery disease has been suggested. The aim of the present study was to investigate the day-night variations in the concentration of soluble vascular cell adhesion molecule-1 (sVCAM-1) in patients with ST-segment elevation myocardial infarction (STEMI) in relation to the light/dark melatonin pattern. Ninety consecutive patients with STEMI who were admitted to the Coronary Care Unit of our institution were studied. We also recruited 70 age- and gender-matched healthy normal subjects. Blood samples were drawn at 09:00 and 02:00 hr, while patients were at rest, for the assessment of sVCAM-1 and melatonin, which were measured using commercially available ELISA. In STEMI patients, melatonin concentrations maintained a diurnal variation, but the difference between nocturnal and diurnal levels was less than that in healthy subjects (P < 0.0001). In contrast to findings with melatonin, sVCAM-1 levels showed no diurnal variations in control subjects. In the STEMI group, however, sVCAM-1 concentration at 02:00 hr was significantly higher than that during the light phase (09:00 hr; 1391 +/- 38 versus 1200 +/- 43 ng/mL, P < 0.05). The results suggest that diurnal variations in endogenous sVCAM-1 production in STEMI patients might be related to an attenuated circadian secretion of melatonin.

Modern and effective therapeutic possibilities have improved the management and outcomes in acute coronary syndromes and acute myocardial infarction. However, substantial morbidity and mortality still remain. Myocardial ischemia-reperfusion injury may contribute to additional damage to myocardial necrosis and apoptosis. Therefore, it has been focused on attention and field of therapeutic actions in the last years. The main mechanisms involved in the pathogenesis of ischemia-reperfusion injury are depressed energy metabolism, elevated oxidative damage, and altered calcium homeostasis. In experimental trials, a variety of drugs have proved effectiveness for the prevention and treatment of the ischemia-reperfusion injury. However, its efficacy, not always confirmed, has not yet been established in clinical practice. On the basis of the strong evidence linking potassium ATP dependent channels opening in the myocardium and its proved cardioprotective role during ischemia, these channels have been pointed out as possible and promising pharmacological targets in this setting. Some evidences suggest that the calcium sensitizing agent levosimendan may have of beneficial and exerts cardioprotective effects on myocardial ischemia and ischemia-reperfusion injury. Further investigation is warranted on this novel application of levosimendan.

Background: Experimental studies have documented the beneficial effects of the endogenously produced antioxidant, melatonin, in reducing tissue damage and limiting cardiac pathophysiology in models of experimental ischemia-reperfusion. Melatonin confers cardioprotection against ischemia-reperfusion injury most likely through its direct free radical scavenging activities and its indirect actions in stimulating antioxidant enzymes. These actions of melatonin permit it to reduce molecular damage and limit infarct size in experimental models of transient ischemia and subsequent reperfusion., Study Design: The Melatonin Adjunct in the acute myocaRdial Infarction treated with Angioplasty (MARIA) trial is an unicenter, prospective, randomized, double-blind, placebo-controlled, phase 2 study of the intravenous administration of melatonin. The primary efficacy end point of this study is to determine whether melatonin treatment reduces infarct size determined by the cumulative release of alpha-hydroxybutyrate dehydrogenase (area under the curve: 0 to 72 h). Other secondary end points will be the clinical events occurring within the first 90 days: death, sustained ventricular arrhythmias, resuscitation from cardiac arrest, cardiogenic shock, heart failure, major bleedings, stroke, need for revascularization, recurrent ischemia, re-infarctions and rehospitalization., Implications: The MARIA trial tests a novel pharmacologic agent, melatonin, in patients with acute myocardial infarction and the hypothesis that it will confer cardioprotection against ischemia-reperfusion injury. If successful, the finding would support the use of melatonin in therapy of ischemic-reperfusion injury of the heart.

Introduction: The aims of the present study were to characterize the day/night variation of matrix metalloproteinase (MMP)-9 in patients who have developed ST-segment elevation myocardial infarction (STEMI), in response to light/dark differences in circulating melatonin and to assess whether melatonin, a day/night variation regulator, modulates the nocturnal inflammatory changes in patients who have STEMI., Methods: The study included 75 patients diagnosed with STEMI and 75 control subjects. Each subject was studied under strictly controlled light/dark conditions. Blood samples for measurement of MMP-9 and melatonin were collected at 09:00 a.m. (light period) and 02:00 a.m. (dark period)., Results: In patients with STEMI, melatonin concentrations maintained a light/dark variation but the difference between nocturnal and diurnal levels was smaller than that in controls (p<0.001). In contrast to melatonin, serum MMP-9 concentrations showed no day/night variation in control subjects. MMP-9 concentrations were significantly higher in patients with STEMI than in control subjects. In the STEMI subjects, MMP-9 serum concentrations in the light period were significantly higher than those during the dark phase (291.1+/-59.5 vs. 261.8+/-57.8 ng/ml, p<0.01). Furthermore in the control subjects there was no correlation between MMP-9 and melatonin levels, while in the STEMI group there was a significant correlation between these parameters (Pearson's r=0.40, p<0.0004)., Conclusions: Our results suggest that the light/dark variations in endogenous MMP-9 production in patients who have STEMI might be associated, at least in part, to the day/night variation of melatonin.

Introduction: The balance between pro-inflammatory and anti-inflammatory molecules is likely to modulate the processes that lead to atherogenesis and rapid coronary artery disease progression. We sought to compare the positive predictive values of serum soluble CD40 ligand (sCD40L)/interleukin-10 (IL-10) ratio, versus individual sCD40L, and IL-10 measurements regarding in-hospital events in patients admitted into the hospital with ST-segment elevation myocardial infarction (STEMI)., Methods: We recruited 96 patients with STEMI. sCD40L and IL-10 were measured at hospital admission in every patient. The composite of in-hospital death and heart failure represented the study end-point. Heart failure was defined as Killip class>1. Multivariable logistic regression analysis was performed to identify independent variables related to in-hospital events., Results: Thirty two patients (33%) achieved the study end-point and 64 (67%) had no adverse events during hospital admission. IL-10 levels (pg/ml) were lower (28.2+/-9.8 versus 33.24+/-11.3, p=0.03) and sCD40L levels (pg/ml) higher (156.8+/-54.2 versus 135.4+/-38.70, p=0.02) in patients with events compared to those without events. Significantly higher odd ratios were found for sCD40L/IL-10 ratio (OR=2.10, 95% CI: 1.90 to 2.80, p=0.01) compared to individual sCD40L (OR=1.40, 95% CI: 0.90 to 2.20, p=0.08) and IL-10 (OR=0.70, 95% CI: 0.50 to 0.93, p=0.02) measurements., Conclusion: Our study showed that serum ratio of sCD40L/IL-10 is a better independent predictor of in-hospital adverse events than individual sCD40L and IL-10 measurements in patients with STEMI.

We evaluated the possible relation between circulating levels of nocturnal melatonin, C-reactive protein, and the development of adverse cardiovascular events in patients with ST-segment elevation myocardial infarction. Patients who had developed adverse events during follow-up had significantly lower nocturnal melatonin levels than patients without events.

C-reactive protein, a marker of inflammation, is increasingly measured to stratify risk for coronary artery disease and guide clinical management. Likewise, a relation has been suggested between decreased nocturnal melatonin levels and coronary artery disease. However, little is known about the association between melatonin and C-reactive protein in patients with ischemic heart disease.

This study was designed to investigate the relationship between nocturnal serum melatonin (MEL) levels and oxidized low-density lipoprotein (OxLDL) in patients with acute coronary syndrome (ACS). OxLDL plays a pivotal role in the development of atherosclerosis. Patients with coronary heart disease have an impaired nocturnal secretion of MEL. To date, there are no clinical human studies concerning the relationship of MEL to low-density lipoprotein (LDL) oxidation in patients with acute myocardial infarction (AMI). The study population contained 60 patients with AMI and 60 control subjects. Levels of circulating OxLDL were measured by a monoclonal antibody 4E6-based competition ELISA. Levels of circulating MEL were measured by an enzyme-immunoassay kit after chloroform extraction. Comparison of levels between AMI and controls, adjusted for age, revealed significantly higher nocturnal serum OxLDL levels (95.47+/-6.81 versus 68.35+/-4.07 U/l; p=0.004) in the AMI subjects. Nocturnal serum levels of MEL were lower in AMI than the control group (20.97+/-3.90 versus 53.19+/-7.80 pg/ml; p=0.009). Serum levels of total, high-density lipoprotein (HDL), and LDL cholesterol did not differ between the groups. Multiple regression analysis was performed on cases to study the association between AMI and serum levels of OxLDL and MEL (OR: 2.93; 95% CI, 2.89-2.98, p=0.01 and OR: 0.94; 95% CI, 0.89-0.97, p=0.02, respectively). This study demonstrates for the first time an independent association between nocturnal levels of OxLDL and MEL in patients with AMI. Additional population studies are necessary to further document these.

Background: Currently available evidence suggests a potentially protective role for interleukin (IL)-10 in atherosclerosis. Reactive oxygen species, such as superoxide anion, hydrogen peroxide, peroxynitrite, and hydroxyl radical, seem to play a pivotal role in the pathogenesis of ischemia-reperfusion injury. The aim of this study was to assess whether a rise in lipid peroxidation (LPx), as malondialdehyde (MDA) and 4 hydroxyalkenal (4-HNE), during acute myocardial infarction (AMI) is associated with serum concentrations of IL-10., Methods: A total of 50 patients diagnosed with AMI and 50 control subjects were studied. Primary angioplasty was performed in the 50 patients with an indication for reperfusion. Serum IL-10 and LPx (MDA + 4-HNE) concentrations were measured using commercially available enzyme-immunoassays. The venous blood samples were taken 90 +/- 35 min after having obtained a TIMI III flow in patients with AMI. In control subjects, blood samples were taken at the time of admission to hospital., Results: IL-10 concentrations were higher in patients with AMI compared with control subjects (32.45 +/- 2.17 vs. 22.10 +/- 2.40 pg/ml; P = 0.03). Serum LPx concentrations were higher in the AMI group (22.20 +/- 3.63 vs. 11.90+/-1.26 microM; P=0.01). IL-10 levels in patients with AMI were significantly correlated with the concentrations of LPx (Pearson's r =0.49, P = 0.02)., Conclusions: Our results provide evidence that (1) IL-10 is increased in a human model of myocardial ischemia-reperfusion and (2) reperfusion injury and elevated IL-10 levels are related in patients with AMI treated with primary percutaneous transluminal coronary angioplasty.

Objective: The purpose of this study was to assess whether serum levels of pregnancy-associated plasma protein A (PAPP-A) are elevated early in patients with acute myocardial infarction (AMI)., Design and Methods: We measured serum levels of PAPP-A in 80 patients with AMI and in 80 age-matched healthy control subjects. The mean (+/-SEM) time from onset of symptoms to blood sampling was 6.3 +/- 2.8 h in the group with AMI., Results: The PAPP-A levels did not differ between the control group and the AMI group (1.24 +/- 0.07 vs. 1.29 +/- 0.02 mIU/l; P = 0.54)., Conclusions: Measurement of serum PAPP-A does not seem to be a useful early marker for AMI.

Aims: Atherosclerosis is a chronic disease that, from its origin to its ultimate complications, involves inflammatory cells, inflammatory proteins, and inflammatory responses from vascular cells. It has been demonstrated that cytokine activities are under neuroendocrine control, in part exerted by the pineal gland through the circadian secretion of its main product melatonin. Melatonin is mainly released during the night, but the precise relationship between melatonin and the light/dark rhythm of interleukin-6 in patients with acute myocardial infarction is still unclear., Methods and Results: The study included 60 patients diagnosed with acute myocardial infarction and 60 healthy volunteers whose venous blood samples were collected at 09:00 h (light period) and 02:00 h (dark period). Our results demonstrate that interleukin-6 concentrations presented a light/dark pattern with mean serum concentrations being higher in the acute myocardial infarction group than in the control group (101.26 +/- 13.43 and 52.67 +/- 7.73 pg/ml at 02:00 h, 41.93 +/- 5.90 and 22.98 +/- 4.49 pg/ml at 09:00 h, respectively, p < 0.05). Differences in the day/night changes in melatonin levels in control subjects (48.19 +/- 7.82 at 02:00 h, 14.51+/- 2.36 at 09:00 h, pg/ml) and acute myocardial infarction patients (25.97 +/- 3.90 at 02:00 h, 12.29 +/- 4.01 at 09:00 h, pg/ml) (p < 0.05) were a result of a reduced nocturnal elevation of melatonin in the acute myocardial infarction group., Conclusions: The current findings suggest that the circadian secretion of melatonin may be responsible at least in part for light/dark variations of endogenous interleukin-6 production in patients with acute myocardial infarction. In this study, the melatonin seems to have an anti-inflammatory effect., (Copyright 2004 Elsevier Ltd.)